Benign Prostatic Hyperplasia (BPH), a disease in which prostate epithelial cells grow abnormally and block urine flow, afflicts more than 10 million adult males in the United States, and many millions more throughout the rest of the world. Until relatively recently, surgical intervention was the only treatment of the disease, and even today, surgery is the treatment of last resort, almost inevitably relied upon when other treatments are not, or cease to be, effective. Prostate surgery and recovery therefrom is painful, and the surgery itself may not be effective and poses the risk of serious side effects. For a recent review, see Barry, 2001 (full citations are provided below).
Only two classes of drugs are currently available to treat the symptoms of BPH. One class includes compounds that inhibit production of the active form of testosterone (dihyrdotestosterone or DHT). Use of drugs in this class can cause a loss of libido and loss of muscle mass and tone in males and is associated with an increased occurrence of high grade prostate cancer. In addition, this therapy is limited by the very long delay (months) between first administering the drug and significant reduction in prostate size in the patient. The second class of currently used drugs for BPH, alpha adrenergic blockers, acts by relaxing the smooth muscles, allowing urine to pass through the urethra more freely. While this class of drugs reduces symptoms more rapidly than the first, it does not reduce the size of the prostate or prevent it from growing larger, which can lead to eventual surgical intervention.
Thus, there is a significant, unmet need for drugs that can treat the underlying disease condition of BPH without serious side effects. The present invention meets that need.